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Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16735-40. Epub 2005 Nov 2.

An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency.

Author information

1
Division of Endocrinology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Abstract

The bone wasting induced by estrogen deficiency is, in part, a consequence of increased T cell production of the osteoclastogenic cytokine TNF-alpha. This phenomenon is due to an expansion of T cells, but the responsible mechanism is unknown. We now show that ovariectomy (ovx) disregulates T lymphopoiesis and induces bone loss by stimulating, through a rise in IL-7 levels, both thymic-dependent differentiation of bone marrow-derived progenitors and thymic-independent, peripheral expansion of mature T cells. Attesting to the relevance of the thymic effects, thymectomy decreases by approximately 50% the bone loss and the stimulation of T lymphopoiesis induced by ovx. In contrast, in vivo attenuation of the elevated IL-7 completely prevents the stimulation of T lymphopoiesis and the bone loss that follow ovx. Thus, the disruption of both T cell and bone homeostasis induced by ovx is mediated by IL-7 and due to both the thymic and extrathymic mechanisms. We conclude that IL-7 is a pivotal upstream target through which estrogen regulates hematopoietic and immune functions that are critical for bone homeostasis.

PMID:
16267136
PMCID:
PMC1283799
DOI:
10.1073/pnas.0505168102
[Indexed for MEDLINE]
Free PMC Article

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